1. Field of the Invention
The present invention relates to the oral delivery of parathyroid hormone (PTH). More particularly, the invention is directed to the use of calcitonin in combination with PTH for the oral administration of PTH.
2. Description of the Related Art
PTH studies done in animals and humans with PTH, PTH-related peptides, and PTH analogs have demonstrated its usefulness in increasing bone formation and bone resorption and have prompted interest in its use for the treatment of osteoporosis and related bone disorders. However, the clinical utility of PTH is limited by the occurrence of hypercalcemia, hypercalcuria and nephrolithiasis. The occurrence of these potentially toxic side effects and alterations in calcium metabolism have remained an obstacle to exploiting the benefits of higher dosages of PTH and have required, for safety concerns, that plasma concentrations of the PTH remain within a narrow band. If the hypercalcemic effects, largely mediated by osteoclasts, could be separated from the bone formative effects, largely mediated by osteoblasts, then the therapeutic window for oral PTH therapy could be increased. In contrast to PTH, calcitonins reduce serum calcium concentrations by interacting directly with osteoclasts resulting in reduction in the bone resorptive surface area by osteoclasts and reduction in net bone resorption. Due to a decrease in plasma calcium concentration there is a corresponding decrease in urinary calcium concentrations, a known risk factor for nephrolithiasis. The present invention describes a method for orally administering PTH which broadens the therapeutic window for PTH administration and allows for the oral administration of greater PTH dosages without the potentially toxic hypercalcemic side effects.